1. Chapter 12
The Cell Cycle

2. Overview: The Key Roles of Cell Division
The ability of organisms to produce more of their own kind best distinguishes living things from nonliving matter
The continuity of life is based on the reproduction of cells, or cell division
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3. Figure 12.1
Figure 12.1 How do a cell’s chromosomes change during cell division?

4. Multicellular organisms depend on cell division for
In unicellular organisms, division of one cell reproduces the entire organism
Multicellular organisms depend on cell division for
Development from a fertilized cell
Growth
Repair
Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division
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5. (b) Growth and development
Figure 12.2
100 m
(a) Reproduction
200 m
(b) Growth and development
Figure 12.2 The functions of cell division.
20 m
(c) Tissue renewal

6. Concept 12.1: Most cell division results in genetically identical daughter cells
Most cell division results in daughter cells with identical genetic information, DNA
The exception is meiosis, a special type of division that can produce sperm and egg cells
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7. Cellular Organization of the Genetic Material
All the DNA in a cell constitutes the cell’s genome
A genome can consist of a single DNA molecule (common in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells)
DNA molecules in a cell are packaged into chromosomes
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8. Figure 12.3
Figure 12.3 Eukaryotic chromosomes.
20 m

9. Somatic cells (nonreproductive cells) have two sets of chromosomes
Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division
Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus
Somatic cells (nonreproductive cells) have two sets of chromosomes
Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells
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10. Distribution of Chromosomes During Eukaryotic Cell Division
In preparation for cell division, DNA is replicated and the chromosomes condense
Each duplicated chromosome has two sister chromatids (joined copies of the original chromosome), which separate during cell division
The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached
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11. Sister chromatids Centromere 0.5 m Figure 12.4
Figure 12.4 A highly condensed, duplicated human chromosome (SEM).

12. Once separate, the chromatids are called chromosomes
During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei
Once separate, the chromatids are called chromosomes
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13. Chromosomal DNA molecules
Figure
Chromosomal DNA molecules
Chromosomes 1
Centromere
Chromosome arm
Chromosome duplication (including DNA replication) and condensation 2
Sister chromatids
Figure 12.5 Chromosome duplication and distribution during cell division.
Separation of sister chromatids into two chromosomes 3

14. Eukaryotic cell division consists of
Mitosis, the division of the genetic material in the nucleus
Cytokinesis, the division of the cytoplasm
Gametes are produced by a variation of cell division called meiosis
Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell
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15. Concept 12.2: The mitotic phase alternates with interphase in the cell cycle
In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis
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16. Phases of the Cell Cycle
The cell cycle consists of
Mitotic (M) phase (mitosis and cytokinesis)
Interphase (cell growth and copying of chromosomes in preparation for cell division)
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17. Interphase (about 90% of the cell cycle) can be divided into subphases
G1 phase (“first gap”)
S phase (“synthesis”)
G2 phase (“second gap”)
The cell grows during all three phases, but chromosomes are duplicated only during the S phase
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18. INTERPHASE S (DNA synthesis) G1 Cytokinesis G2 Mitosis
Figure 12.6
INTERPHASE
S (DNA synthesis) G1
Cytokinesis G2
Mitosis
Figure 12.6 The cell cycle.
MITOTIC (M) PHASE

19. Mitosis is conventionally divided into five phases
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis overlaps the latter stages of mitosis
For the Cell Biology Video Myosin and Cytokinesis, go to Animation and Video Files.
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20. Chromosome, consisting of two sister chromatids
Figure 12.7
10 m
G2 of Interphase
Prophase
Prometaphase
Metaphase
Anaphase
Telophase and Cytokinesis
Centrosomes (with centriole pairs)
Chromatin (duplicated)
Early mitotic spindle
Fragments of nuclear envelope
Nonkinetochore microtubules
Aster
Metaphase plate
Cleavage furrow
Nucleolus forming
Centromere
Figure 12.7 Exploring: Mitosis in an Animal Cell
Plasma membrane
Nucleolus
Nuclear envelope
Chromosome, consisting of two sister chromatids
Kinetochore
Kinetochore microtubule
Nuclear envelope forming
Spindle
Centrosome at one spindle pole
Daughter chromosomes

21. The Mitotic Spindle: A Closer Look
The mitotic spindle is a structure made of microtubules that controls chromosome movement during mitosis
In animal cells, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center
The centrosome replicates during interphase, forming two centrosomes that migrate to opposite ends of the cell during prophase and prometaphase
For the Cell Biology Video Spindle Formation During Mitosis, go to Animation and Video Files.
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22. An aster (a radial array of short microtubules) extends from each centrosome
The spindle includes the centrosomes, the spindle microtubules, and the asters
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23. Kinetochores are protein complexes associated with centromeres
During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes
Kinetochores are protein complexes associated with centromeres
At metaphase, the chromosomes are all lined up at the metaphase plate, an imaginary structure at the midway point between the spindle’s two poles
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24. Metaphase plate (imaginary) Sister chromatids Microtubules
Figure 12.8
Centrosome
Aster
Metaphase plate (imaginary)
Sister chromatids
Microtubules
Chromosomes
Kineto- chores
Centrosome
1 m
Overlapping nonkinetochore microtubules
Figure 12.8 The mitotic spindle at metaphase.
Kinetochore microtubules
0.5 m

25. The microtubules shorten by depolymerizing at their kinetochore ends
In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell
The microtubules shorten by depolymerizing at their kinetochore ends
For the Cell Biology Video Microtubules in Anaphase, go to Animation and Video Files.
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26. EXPERIMENT Kinetochore Spindle pole Mark RESULTS CONCLUSION
Figure 12.9
EXPERIMENT
Kinetochore
Spindle pole
Mark
RESULTS
Figure 12.9 Inquiry: At which end do kinetochore microtubules shorten during anaphase?
CONCLUSION
Chromosome movement
Microtubule
Kinetochore
Tubulin subunits
Motor protein
Chromosome

27. Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell
In telophase, genetically identical daughter nuclei form at opposite ends of the cell
Cytokinesis begins during anaphase or telophase and the spindle eventually disassembles
For the Cell Biology Video Microtubules in Cell Division, go to Animation and Video Files.
© 2011 Pearson Education, Inc.

28. Cytokinesis: A Closer Look
In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow
In plant cells, a cell plate forms during cytokinesis
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29. (a) Cleavage of an animal cell (SEM)
Figure 12.10
(a) Cleavage of an animal cell (SEM)
(b) Cell plate formation in a plant cell (TEM)
100 m
Cleavage furrow
Vesicles forming cell plate
Wall of parent cell
1 m
Cell plate
New cell wall
Figure Cytokinesis in animal and plant cells.
Contractile ring of microfilaments
Daughter cells
Daughter cells

30. Chromatin condensing Nucleus 10 m Nucleolus Chromosomes Cell plate 1
Figure 12.11
Chromatin condensing
Nucleus
10 m
Nucleolus
Chromosomes
Cell plate
Figure Mitosis in a plant cell. 1
Prophase 2
Prometaphase 3
Metaphase 4
Anaphase 5
Telophase

31. Binary Fission in Bacteria
Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission
In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart
The plasma membrane pinches inward, dividing the cell into two
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32. Chromosome replication begins. Two copies of origin
Figure
Origin of replication
Cell wall
Plasma membrane
E. coli cell
Bacterial chromosome 1
Chromosome replication begins.
Two copies of origin 2
Replication continues.
Origin
Origin 3
Replication finishes.
Figure Bacterial cell division by binary fission. 4
Two daughter cells result.

33. The Evolution of Mitosis
Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission
Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis
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34. Intact nuclear envelope
Figure 12.13
Bacterial chromosome
(a) Bacteria
Chromosomes
Microtubules
(b) Dinoflagellates
Intact nuclear envelope
Kinetochore microtubule
(c)
Diatoms and some yeasts
Intact nuclear envelope
Figure Mechanisms of cell division in several groups of organisms.
Kinetochore microtubule
(d) Most eukaryotes
Fragments of nuclear envelope

35. Concept 12.3: The eukaryotic cell cycle is regulated by a molecular control system
The frequency of cell division varies with the type of cell
These differences result from regulation at the molecular level
Cancer cells manage to escape the usual controls on the cell cycle
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36. Evidence for Cytoplasmic Signals
The cell cycle appears to be driven by specific chemical signals present in the cytoplasm
Some evidence for this hypothesis comes from experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei
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37. EXPERIMENT Experiment 1 Experiment 2 S G1 M G1 RESULTS S S M M
Figure 12.14
EXPERIMENT
Experiment 1
Experiment 2 S G1 M G1
RESULTS S S M M
Figure Inquiry: Do molecular signals in the cytoplasm regulate the cell cycle?
When a cell in the S phase was fused with a cell in G1, the G1 nucleus immediately entered the S phase—DNA was synthesized.
When a cell in the M phase was fused with a cell in G1, the G1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

38. The Cell Cycle Control System
The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock
The cell cycle control system is regulated by both internal and external controls
The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received
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39. G1 checkpoint Control system S G1 G2 M M checkpoint G2 checkpoint
Figure 12.15
G1 checkpoint
Control system S G1 G2 M
Figure Mechanical analogy for the cell cycle control system.
M checkpoint
G2 checkpoint

40. For many cells, the G1 checkpoint seems to be the most important
If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide
If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase
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41. (a) Cell receives a go-ahead signal.
Figure 12.16 G0
G1 checkpoint G1
Figure The G1 checkpoint. G1
(a) Cell receives a go-ahead signal.
(b) Cell does not receive a go-ahead signal.

42. The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases
Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks)
Cdks activity fluctuates during the cell cycle because it is controled by cyclins, so named because their concentrations vary with the cell cycle
MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G2 checkpoint into the M phase
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43. (b) Molecular mechanisms that help regulate the cell cycle
Figure 12.17 M G1 S G2 M G1 S G2 M G1
MPF activity
Cyclin concentration
Time
(a) Fluctuation of MPF activity and cyclin concentration during the cell cycle G1 S
Figure Molecular control of the cell cycle at the G2 checkpoint.
Cdk
Cyclin accumulation
Degraded cyclin M G2
G2 checkpoint
Cdk
Cyclin is degraded
Cyclin
MPF
(b) Molecular mechanisms that help regulate the cell cycle

44. Stop and Go Signs: Internal and External Signals at the Checkpoints
An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase
Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide
For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture
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45. A sample of human connective tissue is cut up into small pieces.
Figure 12.18 1
A sample of human connective tissue is cut up into small pieces.
Scalpels
Petri dish 2
Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 4
10 m
PDGF is added to half the vessels. 3
Cells are transferred to culture vessels.
Figure The effect of platelet-derived growth factor (PDGF) on cell division.
Without PDGF
With PDGF

46. A clear example of external signals is density-dependent inhibition, in which crowded cells stop dividing
Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide
Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence
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47. Density-dependent inhibition
Figure 12.19
Anchorage dependence
Density-dependent inhibition
Density-dependent inhibition
Figure Density-dependent inhibition and anchorage dependence of cell division.
20 m
20 m
(a) Normal mammalian cells
(b) Cancer cells

48. Loss of Cell Cycle Controls in Cancer Cells
Cancer cells do not respond normally to the body’s control mechanisms
Cancer cells may not need growth factors to grow and divide
They may make their own growth factor
They may convey a growth factor’s signal without the presence of the growth factor
They may have an abnormal cell cycle control system
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49. A normal cell is converted to a cancerous cell by a process called transformation
Cancer cells that are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue
If abnormal cells remain only at the original site, the lump is called a benign tumor
Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors
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50. A tumor grows from a single cancer cell.
Figure 12.20
Lymph vessel
Tumor
Blood vessel
Cancer cell
Glandular tissue
Metastatic tumor 1
A tumor grows from a single cancer cell.
Cancer cells invade neighboring tissue.
Figure The growth and metastasis of a malignant breast tumor. 2 3
Cancer cells spread through lymph and blood vessels to other parts of the body. 4
Cancer cells may survive and establish a new tumor in another part of the body.

51. Recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment
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52. Figure 12.21
Figure Impact: Advances in Treatment of Breast Cancer

53. Telophase and Cytokinesis
Figure 12.UN01 I N T E R P HA S E G1 S
Cytokinesis
Mitosis G2
MITOTIC (M) PHASE
Figure 12.UN01 Summary figure, Concept 12.2
Prophase
Telophase and Cytokinesis
Prometaphase
Anaphase
Metaphase

54. Figure 12.UN02
Figure 12.UN02 Test Your Understanding, question 7

55. Figure 12.UN03
Figure 12.UN03 Appendix A: answer to Figure 12.4 legend question

56. Figure 12.UN04
Figure 12.UN04 Appendix A: answer to Figure 12.8 legend question

57. Figure 12.UN05
Figure 12.UN05 Appendix A: answer to Test Your Understanding, question 7

58. Figure 12.UN06
Figure 12.UN06 Appendix A: answer to Test Your Understanding, question 10